Cardiac hypertrophy is the major cardiac adaptation to increased mechanical work but the specific mechanical determinants and the initiating biochemical processes of hypertrophy are poorly understood. The activity of ornithine decarboxylase (EC.4.1.1.17), the enzyme which initiates polyamine synthesis and may regulate myocardial protein synthesis, is significantly increased prior to the development of cardiac hypertrophy. This research program proposes to determine: a) the mechanical determinants of this increase in cardiac ornithine decarboxylase (ODC) activity; b) the subcellular mechanism for the increased ODC activity, i.e. increased synthesis or enzyme activation; c) if this increase in ODC correlates with any increase in myosin synthesis; and d) the mechanical determinants of cardiac hypertrophy. The proposed experimental model will be the isolated rabbit right ventricular papillary muscle because the mechanical variables of contractility can accurately be controlled, permitting definition of the mechanical determinants first of ODC activity and secondly of myosin synthesis. The development of a quantitative immunoassay of ODC is proposed to determine changes in the amount of ODC in the papillary muscle after a defined period of tension development. If increases in ODC activity correspond to increases in the amount of ODC in the papillary muscle as determined by the immunoassay, then new synthesis may be the suggested subcellular mechanism for increased ODC activity. If they do not correspond, then activation of ODC is likely. If the mechanical determinants of ODC and myosin synthesis are identical in this model, this would suggest that ODC may regulate the early events of cardiac hypertrophy since increased myosin synthesis is an accepted biochemical marker for the development of hypertrophy.